RESUMO
Experimental autoimmune myasthenia gravis (EAMG) was induced in rhesus monkeys using purified acetylcholine receptor (AChR) from Torpedo california. A single dose of 80 micrograms induced antibody formation two weeks after injection. Two subsequent doses at two-week intervals caused clinical signs (anorexia, fatigability, weight loss, ptosis and dysphagia) which initially responded to treatment with neostigmine. Histologic examination of post-mortem tissues revealed lesions characteristic of myasthenia gravis in man: muscular atrophy, fibrous degeneration and lymphocytic infiltration. Antibodies were quantitated in the sera of three other monkeys which received only 60 micrograms of purified AChR. Abnormally high titers persisted for two years (60-200 micrograms /ml versus 0-10 micrograms/ml for controls). A monkey injected with 60 micrograms AChR as part of reconstituted membrane vesicles had lower titers (30-50 micrograms/ml) than those which received purified receptor. Only those monkeys with antibody titers exceeding 800 micrograms/ml developed overt disease. These titers were 4-100 times higher than those reported for myasthenic humans. The antibody-antigen molar ratios were higher for monkeys with disease than for asymptomatic animals. These data suggest that the diversity of antibody molecules synthesized by the sensitized monkeys determined the appearance of clinical signs, and that the cross reaction of anti-torpedo antibodies with monkey receptor was primarily responsible for the development of EAMG.
Assuntos
Miastenia Gravis/imunologia , Testes de Aglutinação , Animais , Formação de Anticorpos , Macaca mulatta/imunologia , Receptores Colinérgicos/imunologia , Torpedo/imunologiaRESUMO
Experimental autoimmune myasthenia gravis (EAMG) was induced in thesus monkeys using purified acetylcholine recptor (AChR) from Torpedo california. A single dose of 80 µg induced antibody formation two weeks after injection. Two subsequent doses at two-week intervals caused clinical signs (anorexia, fatigability, weight loss, ptosis and dysphagia) which initially responded to treatment with neostigmine. Histologic examination of post-mortem tissues revealed lesions characteristic of myasthenia gravis in man: musuclar atrophy, fibrous degeneration and lymphocytic infiltration. Antibodies were quantitated in the sera of three other monkeys which received only 60 µg of purified AChR. Abnormally high titers persisted for two years (60-200µg/ml versus 0-10µg/ml for controls). A monkey injected with 60µgAChR as part of reconstituted membrane vesicles had lower titers (30-50µg/ml) than those which received purified receptor. Only those monkeys with antibody titers exceeding 800 µg/ml developed overt disease. These titers were 4-100 times higher than those reported for myasthenic humans. The antibody-antigen molar ratios were higher for monkeys with disease than for asymptomatic animals. These data suggest that the diversity of antibody molecules synthesized by the sensitized monkeys determined the appearance of clinical signs, and that the cross reaction of tanti-torpedo antivodies with monkey receptor was primarily responsible for the development of EAMG